Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disease in which aberrant repair processes lead to lung scarring and eventual death. Lung transplantation remains the only viable treatment option to date. Innovative disease models based on human tissue are expected to significantly accelerate the translation of new, urgently needed treatment therapies.
Researchers at the DZL site in Munich (Burgstaller Lab/Schiller Lab) have therefore chosen an innovative approach using a human fibrosis model in the form of precision cut sections of living human lung tissue (PCLS) combined with the state-of-the-art method of single cell transcriptomics.
Basis for more targeted therapies
The analysis provides insights into the different types of cells involved in the early stages of pulmonary fibrosis when lung tissue forms scars. This identified potential drug targets that could be used to treat this disease. In addition, certain drugs were found to affect specific cell types in the lungs, which is important for developing targeted treatments.
In the future, the goal is to increase the analysis throughput for more compounds substantially. In conjunction with AI models, this is expected to speed up the development and implementation of new anti-fibrotic drugs many times over.
Ex vivo tissue perturbations coupled to single-cell RNA-seq reveal multi-lineage cell circuit dynamics in human lung fibrogenesis. Niklas J. Lang, Janine Gote-Schniering, Diana Porras-Gonzalez, Lin Yang, Laurens J. De Sadeleer, R. Christoph Jentzsch, VladimirA. Shitov, Shuhong Zhou, Meshal Ansari, Ahmed Agami, Christoph H. Mayr, Baharak Hooshiar Kashani, Yuexin Chen, LukasHeumos, Jeanine C. Pestoni, Emiel Geeraerts, Vincent Anquetil, Laurent Saniere, Melanie Wögrath, Michael Gerckens, Rudolf Hatz, Nikolaus Kneidinger, Jürgen Behr, Wim A. Wuyts, Mircea-Gabriel Stoleriu, Malte D. Luecken, Fabian J. Theis, GeraldBurgstaller, Herbert B. Schiller. bioRxiv 2023.01.16.524219; doi: https://doi.org/10.1101/2023.01.16.524219